scholarly journals IMMUNOHISTOCHEMICAL AND GENETIC PROGNOSTIC FACTORS OF NEOADJUVANT CHEMORADIOTHERAPY EFFICАCY IN PERSONALIZED TREATMENT OF LOCAL ADVANCED RECTAL CANCER

2020 ◽  
Vol 73 (3) ◽  
pp. 589-596
Author(s):  
Vitalii V. Zvirych ◽  
Yuriy I. Michailovich ◽  
Oleksandr І. Gorbach ◽  
Natalia М. Khranovska
Keyword(s):  
Rectal Cancer ◽  
Protein Expression ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Expression Level ◽  
Protein Expression Level ◽  
Ki 67 ◽  
Mthfr Polymorphism ◽  
Tumour Relapse ◽  
Local Advanced

The aim: The aim of our study was to define the factors that can robustly predict a response to neoadjuvant chemoradiotherapy (NCRT) in patients with local advanced rectal cancer (LARC) and prognosis factors of progression free survival (PFS) using molecular (8-oxodGu), immunohystochemical (Ki-67) and genetic (GSTP1 and MTHFR genes polymorphism) markers. Materials and methods: GSTP1 and MTHFR polymorphisms were studied by real-time PCR on tumour material from 110 patients with LARC. Ki-67 protein expression was assessed using rabbit monoclonal antibodies to Ki-67 (Dako, Denmark) on EnVisionTM FLEX detection system (Dako, Denmark). 8-oxodGu level in eluate was measured by spectrophotometry. Results: Patients from both groups showed significant pathomorphological response to NCRT. It is robust correlation between 8-oxodGu levels in patients’ blood and their response to CRT (mrTRG scale) in MG was determined. Oxaliplatin-containing chemotherapy promotes statistically significant decrease of 8-oxodGu levels. With the decrease of Ki-67 protein expression level the probability of tumour relapse increases. It is determined that critical value of Ki-67 protein expression level makes less than 27 and tumour relapse probability in this case makes 50%. Tumour relapse risk in patients with GSTP1 and MTHFR polymorphism is 12.3 and 16.3 times higher than in patients who do not carry such polymorphism, respectively. Combination of GSTP1, МTНFR polymorphisms and Кі-67 protein expression factors determines prognostic probability of tumour relapse within 51-99%. Conclusions: 8-oxodGu level can serve as independent prognostic factor of NCRT efficacy in patients with LARC. Combination of GSTP1, МTНFR genes polymorphism with Кі-67 protein expression decrease enables monitoring and robust prognosis of LARC relapse.

scholarly journals BMI May Be a Prognostic Factor for Local Advanced Rectal Cancer Patients Treated with Long-Term Neoadjuvant Chemoradiotherapy

2020 ◽  
Vol Volume 12 ◽  
pp. 10321-10332
Author(s):  
Hengchang Liu ◽  
Ran Wei ◽  
Chunxiang Li ◽  
Zhixun Zhao ◽  
Xu Guan ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Prognostic Factor ◽  
Cancer Patients ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Local Advanced

scholarly journals Molecular and Dynamic Evaluation of Proteins Related to Resistance to Neoadjuvant Treatment with Chemoradiotherapy in Circulating Tumor Cells of Patients with Locally Advanced Rectal Cancer

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1539
Author(s):  
Virgílio Souza e Silva ◽  
Emne Ali Abdallah ◽  
Bianca de Cássia Troncarelli Flores ◽  
Alexcia Camila Braun ◽  
Daniela de Jesus Ferreira Costa ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Tumor Cells ◽  
Circulating Tumor Cells ◽  
Transforming Growth Factor ◽  
Locally Advanced ◽  
Neoadjuvant Treatment ◽  
Neoadjuvant Chemoradiotherapy ◽  
Disease Free Survival ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer

The heterogeneity of response to neoadjuvant chemoradiotherapy (NCRT) is still a challenge in locally advanced rectal cancer (LARC). The evaluation of thymidylate synthase (TYMS) and RAD23 homolog B (RAD23B) expression in circulating tumor cells (CTCs) provides complementary clinical information. CTCs were prospectively evaluated in 166 blood samples (63 patients) with LARC undergoing NCRT. The primary objective was to verify if the absence of RAD23B/TYMS in CTCs would correlate with pathological complete response (pCR). Secondary objectives were to correlate CTC kinetics before (C1)/after NCRT (C2), in addition to the expression of transforming growth factor-β receptor I (TGF-βRI) with survival rates. CTCs were isolated by ISET and evaluated by immunocytochemistry (protein expression). At C1, RAD23B was detected in 54.1% of patients with no pCR and its absence in 91.7% of patients with pCR (p = 0.014); TYMS− was observed in 90% of patients with pCR and TYMS+ in 51.7% without pCR (p = 0.057). Patients with CTC2 > CTC1 had worse disease-free survival (DFS) (p = 0.00025) and overall survival (OS) (p = 0.0036) compared with those with CTC2 ≤ CTC1. TGF-βRI expression in any time correlated with worse DFS (p = 0.059). To conclude, RAD23B/TYMS and CTC kinetics may facilitate the personalized treatment of LARC.

scholarly journals Comprehensive Analysis of ESRRA in Endometrial Cancer

2021 ◽  
Vol 20 ◽  
pp. 153303382199208
Author(s):  
Shufang Wang ◽  
Xinlong Huo
Keyword(s):  
Endometrial Cancer ◽  
Protein Expression ◽  
Immune Cell ◽  
Enrichment Analysis ◽  
Gene Set Enrichment Analysis ◽  
The Cancer Genome Atlas ◽  
Expression Level ◽  
Operating Characteristics ◽  
Protein Expression Level ◽  
Normal Tissues

Background: Estrogen-related receptor alpha (ESRRA) was reported to play an important role in multiple biological processes of neoplastic diseases. The roles of ESRRA in endometrial cancer have not been fully investigated yet. Methods: Expression data and clinicopathological data of patients with uteri corpus endometrial carcinoma (UCEC) were obtained from The Cancer Genome Atlas (TCGA). Comprehensive bioinformatics analysis was performed, including receiver operating characteristics (ROC) curve analysis, Kaplan-Meier survival analysis, gene ontology (GO) enrichment analysis, and Gene Set Enrichment Analysis (GSEA). Immunohistochemistry was used to detect the protein expression level of ESRRA and CCK-8 assay was performed to evaluate the effect of ESRRA on the proliferation ability. Results: A total of 552 UCEC tissues and 35 normal tissues were obtained from the TCGA database. The mRNA and protein expression level of ESRRA was highly elevated in UCEC compared with normal tissues, and was closely associated with poor prognosis. ROC analysis indicated a very high diagnostic value of ESRRA for patients with UCEC. GO and GSEA functional analysis showed that ESRRA might be mainly involved in cellular metabolism processes, in turn, tumorigenesis and progression of UCEC. Knockdown of ESRRA inhibited the proliferation of UCEC cells in vitro. Further immune cell infiltration demonstrated that ESRRA enhanced the infiltration level of neutrophil cell and reduced that of T cell (CD4+ naïve), NK cell, and cancer associated fibroblast (CAF). The alteration of immune microenvironment will greatly help in developing immune checkpoint therapy for UCEC. Conclusions: Our study comprehensively analyzed the expression level, clinical value, and possible mechanisms of action of ESRRA in UCEC. These findings showed that ESRRA might be a potential diagnostic and therapeutic target.

Is Metformin Associated With Improved Response to Neoadjuvant Chemoradiotherapy in Locally Advanced Rectal Cancer?

2021 ◽  
Vol 268 ◽  
pp. 465-473
Author(s):  
Pere Planellas ◽  
Lidia Cornejo ◽  
Jose Ignacio Rodríguez-Hermosa ◽  
Eloy Maldonado ◽  
Ander Timoteo ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Locally Advanced ◽  
Neoadjuvant Chemoradiotherapy ◽  
Advanced Rectal Cancer ◽  
Locally Advanced Rectal Cancer
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